神经发育障碍和不同类型癌症中的赖氨酸乙酰转移酶6复合物

Lysine Acetyltransferase 6 Complexes in Neurodevelopmental Disorders and Different Types of Cancer.

作者信息

Mousavi Negar, Yang Xiang-Jiao

机构信息

Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.

Department of Medicine, McGill University, Montreal, Quebec, Canada.

出版信息

Results Probl Cell Differ. 2025;75:391-410. doi: 10.1007/978-3-031-91459-1_14.

DOI:10.1007/978-3-031-91459-1_14

PMID:40593218

Abstract

Lysine acetylation is a critical post-translational modification that regulates gene expression and cellular functions. The MYST family lysine acetyltransferases KAT6A (also known as MOZ and MYST3) and KAT6B (a.k.a. MORF and MYST4), in complex with the multivalent epigenetic regulator BRPF1, play key roles in hematopoietic and neural development. Dysregulation of these complexes is implicated in neurodevelopmental disorders, such as Genitopatellar and Say-Barber-Biesecker-Young-Simpson syndromes, as well as in various cancers, including leukemia and medulloblastoma. The evolutionary conservation of these complexes in Drosophila melanogaster and Caenorhabditis elegans underscores their fundamental biological significance. Understanding the structural and functional mechanisms of KAT6-BRPF1 complexes provides insight into their pathological roles and therapeutic potential.

摘要

赖氨酸乙酰化是一种关键的翻译后修饰，可调节基因表达和细胞功能。MYST家族赖氨酸乙酰转移酶KAT6A（也称为MOZ和MYST3）和KAT6B（又名MORF和MYST4）与多价表观遗传调节剂BRPF1形成复合物，在造血和神经发育中起关键作用。这些复合物的失调与神经发育障碍有关，如生殖器髌骨综合征和Say-Barber-Biesecker-Young-Simpson综合征，以及各种癌症，包括白血病和髓母细胞瘤。这些复合物在黑腹果蝇和秀丽隐杆线虫中的进化保守性凸显了它们的基本生物学意义。了解KAT6-BRPF1复合物的结构和功能机制有助于深入了解它们的病理作用和治疗潜力。